Pressure-based mapping of protein conformational landscapes

Résumé :

Protein function depends upon dynamics, and while in recent years great progress has been made in predicting protein structure from sequence, the sequence determinants of functional dynamics have yet to be defined. We have developed an approach using a combination of high-pressure NMR, SAXS, fluorescence, and computation to locally and globally map protein stability and functional dynamics. On a model repeat protein system we find that single amino acid substitutions lead to large changes in local stability and apparent folding cooperativity, while global stabilities of the variant proteins are similar. In the case of the Arf GTPases, which undergo massive conformational changes during their nucleotide switch transition, we demonstrated that the switch mechanism implicates the population of a functional molten globule. Moreover, we discovered the sequence determinants of back-to-front allosteric control of the switch that differentiates switching probabilities of the Arf family members, and likely many other small GTPases.

_

Ces séminaires, ainsi que les soutenances et cours sont ouverts à tous, notez toutefois que l’accès au campus EPN nécessite un avis de rendez-vous. Merci de remplir ce formulaire et de l’adresser, plus de 48h à l’avance, à ce contact. Pensez à vous munir d’une pièce d’identité le jour de votre visite.